Doctor of Pharmacy Pharmacotherapeutics-III
2- Parkinsonism:
Faculty Name: Dr. Sarita Jangra
Parkinson’s disease is a common neurodegenerative disorder that can cause significant
disability and decreased quality of life. The cardinal physical signs of the disease are distal
resting tremor, rigidity, bradykinesia, and asymmetric onset.
What is Parkinson’s disease?
Parkinson’s disease is a neurodegenerative brain disorder that progresses slowly in most
people. Symptoms can take years to develop, and most people live for many years with the
disease. The symptoms caused by Parkinson’s include an ongoing loss of motor control
(resting tremors, stiffness, slow movement, postural instability) as well as a wide range of
non-motor symptoms (such as depression, loss of sense of smell, gastric problems, cognitive
changes and many others).
What is Parkinsonism?
Parkinsonism is a general term that refers to a group of neurological disorders that cause
movement problems similar to those seen in Parkinson’s disease such as tremors, slow
movement and stiffness. Under the category of parkinsonism there are a number of disorders,
some of which have yet to be clearly defined or named. Early in the disease process, it is
often hard to know whether a person has idiopathic (meaning “of unknown origins”)
Parkinson’s disease or a syndrome that mimics it. Parkinsonisms, also known as atypical
Parkinson’s disease or Parkinson’s plus, represent about 10-15% of all diagnosed cases of
parkinsonism. These syndromes tend to progress more rapidly than Parkinson’s, present with
additional symptoms such as early falling, dementia or hallucinations, and do not respond or
respond only for a short time to levodopa therapy.
Drug-Induced Parkinsonism
Drug-induced parkinsonism can be difficult to distinguish from Parkinson’s, though the
tremors and postural instability may be less severe. It is usually the side effect of drugs that
affect dopamine levels in the brain, such as antipsychotics, some calcium channel blockers
and stimulants like amphetamines and cocaine. If the affected person stops taking the drug(s),
symptoms usually subside over time, but may take as long as 18 months to do so.
Progressive Supranuclear Palsy (PSP)
PSP is slightly more common than ALS (also called Lou Gehrig disease). Symptoms usually
begin in the early 60’s. Common early symptoms include loss of balance while walking that
Dr. Sarita Jangra
results in unexplained falls, forgetfulness and personality changes. The visual problems
associated with PSP generally occur 3 to 5 years after the walking problems and involve the
inability to aim the eyes properly because of weakness or paralysis of the muscles that move
the eyeballs. Individuals with PSP may have some response to dopaminergic treatment but
may require higher doses than patients with Parkinson’s disease.
Multiple System Atrophy (MSA)
MSA (also referred to as Shy-Drager syndrome) is the term for a group of disorders in which
one or more systems in the body stop working. In MSA the autonomic nervous system is
often severely affected early in the course of the disease. Symptoms include bladder problems
resulting in urgency, hesitancy or incontinence and orthostatic hypotension (nOH). In nOH
the blood pressure drops so low when standing that fainting or near fainting can occur. When
lying down, the patient’s blood pressure can be quite high. For men, the earliest sign may be
loss of erectile function. Other symptoms that may develop include impaired speech,
difficulties with breathing and swallowing, and inability to sweat.
Vascular Parkinsonism
Vascular parkinsonism is usually caused by clotting in the brain from multiple small strokes.
People with vascular parkinsonism tend to have more problems with gait than tremor and
have more problems in the lower body. The disorder progresses very slowly in comparison to
other types of parkinsonism. Symptoms in vascular parkinsonism may or may not respond to
levodopa.
Dr. Sarita Jangra
Diagnosis
Dr. Sarita Jangra
Early-Stage Treatment
Early-stage Parkinson’s disease includes patients who have had the disease for less than five
years or those who have not developed motor complications from levodopa use.4 Treatment
with monoamine oxidase-B (MAO-B) inhibitors, amantadine (Symmetrel), or
anticholinergics may modestly improve mild symptoms; however, most patients need
levodopa or a dopamine agonist. The American Academy of Neurology (AAN) recommends
levodopa or a dopamine agonist, when dopaminergic treatment is required, depending on the
need to improve motor disability (levodopa is better) or decrease motor complications
(dopamine agonists cause fewer motor complications)
Above table summarizes medications approved for Parkinson’s disease. In general, a
dopamine agonist is initiated in patients with mild disease with onset at a younger age,
whereas levodopa is initiated for older patients with severe motor symptoms.
Dr. Sarita Jangra
levodopa
Levodopa is the most effective pharmacologic agent for Parkinson’s disease and remains the
primary treatment for symptomatic patients. Levodopa is always combined with carbidopa,
because carbidopa prevents peripheral conversion of levodopa to dopamine by blocking dopa
decarboxylase. When combined with levodopa, carbidopa increases cerebral levodopa
bioavailability and reduces the peripheral adverse effects of dopamine (e.g., nausea,
hypotension). Because dopa decarboxylase is saturated by carbidopa at approximately 70 to
100 mg a day, patients receiving less than this amount of carbidopa are more likely to
experience nausea and vomiting. Dosing should start with one 25/100-mg
carbidopa/levodopa (Sinemet) tablet three times a day. Sustained-release preparations add no
benefit for motor complications compared with immediate release preparations
Dopamine agonists
Dopamine agonists directly stimulate dopamine receptors and include bromocriptine
(Parlodel), pergolide (Permax), pramipexole (Mirapex), and ropinirole (Requip). Studies have
demonstrated that dopamine agonists, alone or combined with levodopa, are effective against
early Parkinson’s disease. Double-blind controlled trials comparing ropinirole or pramipexole
with levodopa showed that levodopa was more effective at reducing UPDRS scores than
dopamine agonists; however, these studies also noted a lower incidence of motor
complications with dopamine agonists
Other agents
Anticholinergic agents are commonly used to treat Parkinson’s disease. However, low
effectiveness and a high incidence of gastrointestinal and neuropsychiatric adverse effects
limit their use in older patients. Anticholinergics typically are used in patients younger than
70 years with disabling resting tremors and preserved cognitive function.
Late-Stage Treatment
Late-stage Parkinson’s disease includes patients already receiving carbidopa/levodopa
treatment who have developed motor complications. After five years of treatment with
levodopa, about 40 percent of patients develop motor fluctuations and dyskinesia (i.e.,
involuntary choreiform or stereotypic movements involving the head, trunk, limbs, and,
occasionally, the respiratory muscles)
Dopamine agonists
Systematic reviews have demonstrated that dopamine agonists may significantly reduce “off”
time, improving motor impairment and disability and reducing the need for levodopa.
Parenteral apomorphine (Apokyn), a powerful dopamine agonist, is useful for patients
experiencing a sudden, unexpected, and resistant “off” period. This drug can cause severe
adverse effects and should only be prescribed by those experienced in its complex
administration
Dr. Sarita Jangra
COMT inhibitors COMT inhibitors (e.g., entacapone [Comtan], tolcapone [Tasmar])
decrease the degradation of levodopa and extend its half-life, thus relieving the end-of-dose
wearing-off effect and reducing “off” time.
Surgery
Surgical treatment is becoming more common for Parkinson’s disease because of
advances in brain imaging and neurosurgical techniques. An evidence-based review
concluded that deep brain stimulation of the subthalamic nucleus effectively improves
motor function and reduces motor fluctuations, dyskinesia, and antiparkinsonian
medication use
Nonpharmacologic Treatment
Stretching, strengthening, and balance training may improve gait speed, balance, and
participation in activities of daily living. Nutritional interventions (e.g., a high-fiber diet) can
help reduce constipation. Dietary amino acids may interfere with levodopa absorption;
therefore, protein restriction may be necessary for patients with decreased levodopa response.
There is no evidence supporting the use of vitamin E or other antioxidants. Support and
counseling are essential for patients with Parkinson’s disease. In one study, patient education
was associated with better health-related quality of life
Dr. Sarita Jangra
